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Mechanistic Study of Hetero-Diels–Alder [4 + 2] Cycloaddition Reactions Between 2-Nitro-1H-Pyrrole and Isoprene

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Abstract

Diels–Alder [4 + 2] cycloaddition a reaction between 2-nitro-1H-pyrrole and isoprene was examined within the Molecular Electron Density Theory (MEDT) by employing DFT functional combined with B3LYP/6–31(d). Conceptual DFT (CDFT) analysis allows to characterizing 2-nitro-1H-pyrrole as a nucleophile and isoprene an electrophile, whilst examination of the Parr functions permit explanation the chemo- and regioselectivity observed experimentally in total conformity with the barrier activation. Electron localization function (ELF) topological investigation of some points along intrinsic reaction coordinate (IRC) profile associated with the most favorable reaction channel permits to establish a non-concerted two stage one-step molecular mechanism.

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References

  1. Kim HJ, Ruszczycky MW, Choi SH, Liu YN, Liu HW (2011) Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn a. Nature 473:109–112

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Gao L, Su C, Du X, Wang R, Chen S, Zhou Y, Liu C, Liu X, Tian R, Zhang L, Xie K, Chen S, Guo Q, Guo L, Hano Y, Shimazaki M, Minami A, Oikawa H, Huang N, Houk KN, Huang L, Dai LX (2020) FAD-dependent enzyme-catalysed intermolecular [4+2] cycloaddition in natural product biosynthesis. Nat Chem 12:620–628

    CAS  PubMed  Google Scholar 

  3. Fraley AE, Sherman DH (2020) Enzyme evolution in fungal indole alkaloid biosynthesis. FEBS J 287:1381–1402

    CAS  PubMed  Google Scholar 

  4. Jeffrey DR, Chang CY (2020) Terpene synthases in disguise: enzymology, structure, and opportunities of non-canonical terpene synthases. Nat Prod Rep 37:425–463

    Google Scholar 

  5. Tan D, Jamieson CS, Ohashi M, Tang M-C, Houk KN, Tang Y (2019) Genome-mined diels-alderasecatalyzes formation of the cis-octahydrodecalins of varicidin A and B. J Am ChemSoc 141:769–773

    CAS  Google Scholar 

  6. Hwang S, Kim E, Lee J, Shin J, Yoon YJ, Oh DC (2020) Structure revision and the biosynthetic pathway of tripartilactam. J Nat Prod 83:578–583

    CAS  PubMed  Google Scholar 

  7. Chen Q, Gao J, Jamieson C, Liu J, Ohashi M, Bai J, Yan D, Liu B, Che Y, Wang Y, Houk KN, Hu Y (2019) Enzymatic intermolecular hetero-diels−alder reaction in thebiosynthesis of tropolonicsesquiterpenes. J Am ChemSoc 141:14052–14056

    CAS  Google Scholar 

  8. Paton RS, Mackey JL, Kim WH, Lee JH, Danishefsky SJ, Houk KN (2010) Origins of stereoselectivity in the trans-diels-alder Paradigm. J Am ChemSoc 132:9335–9340

    CAS  Google Scholar 

  9. Gu J, Ma C, Li QZ, Du W, Chen YC (2014) β, γ-Regioselective inverse-electron-demand aza-Diels-Alder reactions with α, β-unsaturated aldehydes via dienamine catalysis. Org Lett 16:3986–3989

    CAS  PubMed  Google Scholar 

  10. Padwa A, Brodney M, Dimitroff M (1997) Diels−alder reaction of 2-amino-substituted furans as a method for preparing substituted anilines. J Org Chem 62:4088–4096

    CAS  Google Scholar 

  11. Pople JA, Schlegel HB, Krishnan R, Defrees DJ, Binkley JS, Frisch MJ, Whiteside RA, Hout R, Hehre W (1981) Molecular orbital studies of vibrational frequencies. Int J Quantum Chem 20:269–278

    Google Scholar 

  12. Dresler E, Jasińska E, Krygier Ł, Bogdan N, Jasiński R (2015) SprzężonenitroalkenyjakokomponentynieuzgodnionychreakcjiDielsa-Aldera– najnowsze. DoniesieniaChemik 69:645–649

    Google Scholar 

  13. Uliana MP, Servilha BM, Alexopoulos O, Oliveira KTD, Tormena CF, Ferreira MAB, Brocksom TJ (2014) TheDielseAlder reactions of para-benzoquinone nitrogen-derivatives: an experimental and theoretical study. Tetrahedron 70:6963–6973

    CAS  Google Scholar 

  14. Lubomír R, Pavel Š, Zdeněk H, Richard H, Pavel Č, Aleš S (2005) An experimental and theoretical study of stereoselectivity of furan-maleic anhydride and furan-maleimide Diels-alder reactions. J Org Chem 70:6295–6302

    Google Scholar 

  15. Radomir J, Magdalena K, Agnieszka ŁK, Agnieszka K, Dresler E, Anna BC (2014) An experimental and theoretical study of the hetero Diels-Alder reactions between (E)-2-aryl-1-cyano-1-nitroethenes and ethyl vinyl ether: one-step or zwitterionic, two-step mechanism? React KinetMechCatal 113:333–345

    Google Scholar 

  16. Domingo LR, Picher MT, Arroyo P (2006) Towards an understanding of the polar Diels-alder reactions of nitrosoalkenes with enamines: a theoretical study. Eur J Org Chem 2006:2570–2580

    Google Scholar 

  17. He M, Struble JR, Bode JWJ (2006) Highly enantioselectiveazadiene Diels-Alder reactions catalyzed by chiral N-heterocyclic carbenes. Am ChemSoc 128:8418–8420

    CAS  Google Scholar 

  18. Simal C, Lebl T, Slawin AMZ, Smith AD (2012) Dihydropyridones: catalytic asymmetric synthesis, N-to C-sulfonyl transfer, and derivatizations. AngewChem 124:3713–3717

    Google Scholar 

  19. Zhao X, Ruhl KE, Rovis T (2012) N-Heterocyclic-carbene-catalyzed asymmetric oxidative hetero-Diels–Alder reactions with simple aliphatic aldehydes. AngewChem 124:12496–12499

    Google Scholar 

  20. Jiang X, Liu L, Zhang P, Zhong Y, Wang R (2013) Catalytic asymmetric β, γ activation of α, β-unsaturated γ-Butyrolactams: direct approach to β, γ-functionalized dihydropyranopyrrolidin-2-ones. AngewChemInt Ed 52:11329–11333

    CAS  Google Scholar 

  21. Sharpless KB, Amberg W, Bennani YL, Crispino GA, Hartung J, Jeong KS, Kwong HL, Morikawa K, Wang ZM, Xu D, Zhang XL (1992) The osmium-catalyzed asymmetric dihydroxylation: a new ligand class and a process improvement. J Org Chem 57:1992–2769

    Google Scholar 

  22. Blokzijl W, Blandamer MJ, Engberts JBFN (1991) Diels-Alder reactions in aqueous solutions. Enforced hydrophobic interactions between diene and dienophile. J Am ChemSoc 113:4241–4246

    CAS  Google Scholar 

  23. Zeroual A, Ríos-Gutiérrez M, Salah M, El Abdallaoui HE, Domingo LR (2019) An investigation of the molecular mechanism, chemoselectivity and regioselectivity of cycloaddition reaction between acetonitrile N-oxide and 2,5-dimethyl-2H-[1,2,3]diazaphosphole: a MEDT study. J ChemSc 131:75

    Google Scholar 

  24. Domingo LR, Ríos-Gutiérrez M, Pérez P (2019) Unveiling the high reactivity of cyclohexynes in [3+2] cycloaddition reactions through the molecular electron density theory. Org BiomolChem 17:498–508

    CAS  Google Scholar 

  25. Zeroual A, Ríos-Gutiérrez M, El Ghozlani M, El Idrissi M, OuledAitouna A, Salah M, El Abdallaoui HE, Domingo LR (2020) A molecular electron density theory investigation of the molecular mechanism, regioselectivity, stereoselectivity and chemoselectivity of cycloaddition reaction between acetonitrile N-oxide and 2,5-dimethyl-2H-[1,2,3]diazarsole. TheorChemAcc 139:37

    CAS  Google Scholar 

  26. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789

    CAS  Google Scholar 

  27. Francl MM, Pietro WJ, Hehre WJ (1982) Self-consistent molecular orbital methods. XXIII. a polarization-type basis set for second-row elements. J ChemPhys 77:3654–3665

    CAS  Google Scholar 

  28. Schlegel HB (1982) Optimization of equilibrium geometries and transition structures. J ComputChem 2:214–218

    Google Scholar 

  29. Frisch MJ et al (2009) Gaussian 09. Gaussian Inc, Wallingford, CT

    Google Scholar 

  30. Parr RG, Szentpaly LV, Liu S (1999) Electrophilicity index. J Am ChemSoc 121:1922–1924

    CAS  Google Scholar 

  31. Domingo LR, Chamorro E, Pérez P (2008) Understanding the reactivity of captodativeethylenes in polar cycloaddition reactions. Theor Study J Org Chem 73:4615–4624

    CAS  Google Scholar 

  32. Domingo LR, Pérez P (2011) The nucleophilicity N index in organic chemistry. Org BiomolChem 9:7168–7175

    CAS  Google Scholar 

  33. Kohn W, Sham L (1965) Self-consistent equations including exchange and correlation effects. J Phys Rev A 140:1133–1138

    Google Scholar 

  34. Zeroual A, Benharref A, El Hajbi A (2015) Theoretical study of stereoselectivity of the [1+2] cycloaddition reaction between (1S,3R,8S)-2,2-dichloro-3,7,7,10-tetramethyltricyclo[6,4,0,01.3]dodec-9-ene and dibromocarbene using density functional theory (DFT) B3LYP/6-31G*(d). J Mol Model 21:2594–2599

    Google Scholar 

  35. El Idrissi M, El Haib A, Zoubir M, Hammal R, Zeroual A, Hajbi EL, A, (2016) A DFT computational study on the molecular mechanism of reaction between methyl 3-hydroxy-3-methyl-2 methylene butanoate and (E)-N-methyl-1-phenylethan-1-imine oxide. JCMMD 6:75–79

    Google Scholar 

  36. Ourhriss N, Zeroual A, Ait Elhad M, Mazoir N, Abourriche A, Gadhi CA, Benharref A, El Hajbi A (2017) Synthesis of 1-isopropyl-4,7-dimethyl-3-nitronaphthalene: an experimental and theoretical study of regiospecific nitration. JMES 8:1385–1390

    CAS  Google Scholar 

  37. Zoubir M, Zeroual A, El Idrissi M, El Haib A, Moumou M, Hammal R, Mazoir N, Benharref A, El Hajbi A (2017) the thermodynamic aspect, the temperature and the solvent effects on the chemical reactivity of the darzens reaction between isobutyraldehyde and isopropyl dibromoacetate: DFT study. JMES 8:990–996

    CAS  Google Scholar 

  38. El Idrissi M, Zoubir M, Zeroual A, El Ajlaoui R, El Haib A, Benharref A, Elhajbi A (2016) A theoretical study of the mechanism and regioselectivity of the 1,3-dipolar cycloaddition reaction of azides with alkynes. J Mar ChimHeterocycl 15:145–151

    Google Scholar 

  39. Zeroual A, Hammal R, Benharref A, El Hajbi A, Mazoir N (2016) A theoretical investigation of the reactivity and regioselectivity of triterpene derivatives using difference local index, Parr functions. Mor J Chem 4:938–944

    CAS  Google Scholar 

  40. Fukui K (1970) Formulation of the reaction coordinate. J PhysChem 74:4161–4163

    CAS  Google Scholar 

  41. Tomasi J, Persico M (1994) Formulation of the reaction coordinate. Chem Rev 94:2027–2094

    CAS  Google Scholar 

  42. Becke AD, Edgecombe KE (1990) A simple measure of electron localization in atomic andmolecular systems. J ChemPhys 92:5397–5403

    CAS  Google Scholar 

  43. Noury S, Krokidis X, Fuster F, Silvi B (1999) Computational tools for the electron localization function topological analysis. ComputChem 23:597–604

    CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Technology, Sultan Moulay Slimane University, Beni-Mellal, Morocco

    Mohamed El Ghozlani

  2. Molecular Modeling and Spectroscopy Research Team, Faculty of Science, Chouaïb Doukkali University, P.O. Box 20, 24000, El Jadida, Morocco

    Ali Barhoumi, Anas Ouled Aitouna, Abdellah Zeroual & Mohammed El Idrissi

  3. Faculty of Sciences and Technology, Equipe Procédés Agro-Industriels Environnementaux Sultan Moulay Slimane University, Beni-Mellal, Morocco

    Reda Elkacmi

  4. Department of Chemistry, Multidisciplinary Faculty, Sultan Moulay Slimane University, P.O. Box 591, Béni-Mellal, Morocco

    Mohammed El Idrissi

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  1. Mohamed El Ghozlani
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Correspondence to Mohamed El Ghozlani.

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El Ghozlani, M., Barhoumi, A., Elkacmi, R. et al. Mechanistic Study of Hetero-Diels–Alder [4 + 2] Cycloaddition Reactions Between 2-Nitro-1H-Pyrrole and Isoprene. Chemistry Africa 3, 901–909 (2020). https://doi.org/10.1007/s42250-020-00187-8

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  • DOI: https://doi.org/10.1007/s42250-020-00187-8

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